Enema dispenser

ABSTRACT

An enema includes a liquid in a dispenser having a bottle, a nozzle attached to the bottle, and a valve. The valve may be a membrane having a slit and a thickness of at most 0.90 mm. The valve may be attached to the bottle or it may be attached to the nozzle. The enema can be administered more easily, with a lower amount of force. A method of bowel cleansing includes inserting the enema into a rectum and applying a compression force to the enema bottle.

BACKGROUND

Bowel cleansing procedures typically involve the purging of the colonusing an enema. An enema may be packaged as an over-the-countertherapeutic product for use by a consumer. Such a ready-to-use enemaincludes a liquid in a dispenser, which is typically a flexible bottleequipped with a nozzle. The liquid is administered by inserting thenozzle into the rectum of the patient, and squeezing the bottle to forcethe liquid through the nozzle and into the patient's colon.

The force required to squeeze the liquid from an enema dispenser affectsthe ease with which a user may administer the liquid. Theself-administration of a conventional enema may be especially difficultfor elderly patients, due to the squeeze force required to deliver acomplete dose of the enema liquid. Although it would be advantageous todecrease the amount of squeeze force required to administer an enema,such a modification may adversely affect other desirable features of theproduct. In particular, it is desirable to prevent any reflux of liquidback into the bottle after the enema liquid has been delivered, and itis desirable to prevent leakage of the enema liquid from the dispenserprior to use. A simple reduction in the resistance to flow of the liquidthrough the dispenser may compromise these features.

It is desirable to provide an enema that is easier to administer, andthat prevents reflux of liquid into the bottle after use and leakage ofthe enema liquid prior to use. It is also desirable to provide enemadispensers that can be used to more easily administer a variety ofdifferent enema liquids. It is also desirable to provide enemadispensers that can be used to more easily administer a range of dosesof enema liquids.

SUMMARY

In one aspect, the invention provides a valve including a membranehaving a slit and a thickness from 0.05 to 0.90 millimeter (mm).

In yet another aspect, the invention provides a nozzle including aproximal opening, a distal opening, and a lumen between the proximalopening and the distal opening; and a valve, as described above,attached to the nozzle and extending across the lumen.

In yet another aspect, the invention provides a dispenser including abottle having a bottle opening; a nozzle, attached to the bottle at thebottle opening; and a valve, as described above. The nozzle includes aproximal opening, a distal opening, and a lumen between the proximalopening and the distal opening.

In yet another aspect, the invention provides an enema including abottle having a bottle opening; a nozzle, attached to the bottle at thebottle opening; a liquid in the bottle; and a valve, as described above.The nozzle includes a proximal opening, a distal opening, and a lumenbetween the proximal opening and the distal opening;

In yet another aspect, the invention provides an enema including abottle having a bottle opening; a nozzle, attached to the bottle at thebottle opening and having a distal opening; and a liquid in the bottle.At least a portion of the liquid can be dispensed through the distalopening when the bottle is compressed with a force of at most 15Newtons.

In yet another aspect, the invention provides an enema including abottle having a bottle opening; a nozzle, attached to the bottle at thebottle opening and having a distal opening; and at least a unit dose ofa liquid in the bottle. At least 50% of the unit dose can be dispensedthrough the distal opening when the bottle is compressed with a force ofat most 60 Newtons.

In yet another aspect, the invention provides an enema including a meansfor containing a liquid; a means for delivering at least a unit dose ofthe liquid to a colon; a means for preventing flow of the liquid fromthe containing means to the colon until a compression force of at most15 Newtons is applied to the containing means; and a means forpreventing liquid flow from the colon into the containing means.

In yet another aspect, the invention provides method of bowel cleansingincluding inserting an enema as described above into a rectum, andapplying a compression force to the bottle.

The following definitions are included to provide a clear and consistentunderstanding of the specification and claims.

The term “membrane” means a flexible sheet of material having athickness dimension less than 10% of its width or length dimensions.

The term “proximal,” with respect to an enema and/or its components,means a position or direction that would be away from the body of thepatient when the enema is administered.

The term “distal,” with respect to an enema and/or its components, meansa position or direction that would be toward or inside the body of thepatient when the enema is administered.

The term “lumen” means a passageway through which liquid may flow.

The term “squeeze force” means the compression force required to squeezea particular volume of liquid from a dispenser through a distal openingof the dispenser.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention can be better understood with reference to the followingdrawings and description. The components in the figures are notnecessarily to scale, emphasis instead being placed upon illustratingthe principles of the invention.

FIG. 1 is a side representation of an enema.

FIG. 2 is a side representation of a bottle.

FIG. 3 is a side cross section representation of a nozzle.

FIG. 4 is a side cross section representation of a nozzle containing twopieces.

FIG. 5 is a side cross section representation of an enema.

FIG. 6A is a top representation of a valve, and FIG. 6B is a siderepresentation of the valve.

FIG. 7A-E are top representations of valves.

FIG. 8 is a graph of average squeeze force measurements for salineenemas for adult use (133 mL).

FIG. 9 is a graph of average squeeze force measurements for salineenemas for adult use (240 mL).

FIG. 10 is a graph of average squeeze force measurements for salineenemas for pediatric use (66 mL).

FIG. 11 is a graph of average squeeze force measurements for bisacodylenemas for adult use.

FIG. 12 is a graph of average squeeze force measurements for mineral oilenemas for adult use.

FIG. 13 represents a method of bowel cleansing.

DETAILED DESCRIPTION

The present invention provides an enema that can be administered with alower amount of force. The enema includes a liquid in a dispenser havinga bottle, a nozzle attached to the bottle, and a valve. The valve may bea membrane having a slit and a thickness of at most 0.90 millimeter(mm). The valve may be attached to the bottle or may be attached to thenozzle. The present invention also includes a method of bowel cleansing,including inserting the enema into a rectum and applying a compressionforce to the enema bottle.

It has been surprisingly found that a valve having a thickness less thanthe conventional thickness may provide for a reduction in the squeezeforce required to dispense a liquid from an enema dispenser. Althoughthe liquid may experience a lower resistance to flow duringadministration, there may be little or no increase in reflux of liquidback into the enema bottle after the enema liquid has been administered.In addition, there may be little or no increase in leakage of the enemaliquid prior to administration. The dispenser design may provide theseadvantageous properties for a variety of enema liquids and for a rangeof doses of these liquids.

FIG. 1 represents an enema 100 including an enema dispenser 110, anenema liquid 120 in the dispenser, and optional shield 130. Thedispenser 110 includes a bottle 112 and a nozzle 114. The bottle 112 mayhave a variety of shapes and sizes, and preferably contains a unit doseof the enema liquid 120. The nozzle 114 is attached to the bottle 112 atthe opening of the bottle, and includes a passageway for the enemaliquid. At least a portion of the exterior of the nozzle 114 may have alubricant to facilitate proper insertion of the nozzle into the patient.The shield 130 fits over the nozzle 114, protecting the nozzle and/orsealing the dispenser prior to use. The shield may help maintain alubricant in place on the nozzle prior to use.

The enema liquid 120 may be any liquid that promotes a bowel movementwhen introduced into the colon. Examples of enema liquids include water;hypertonic aqueous salt solutions; solutions or suspensions of catharticagents, such as bisacodyl or phenolphthalein; and mineral oil.Preferably a unit dose of the enema liquid 120 is present in the bottle112 of the dispenser 110. The volume of the unit dose depends on thetype of enema liquid, the specific formulation of active and inactiveingredients in the liquid, and the type of patient for which the enemais intended. Preferably the total volume of the enema liquid 120 in thebottle 112 is greater than the volume of the unit dose, since a smallamount of the liquid typically remains in the bottle after the enema hasbeen administered to the patient.

In one example, the enema liquid 120 is a hypertonic aqueous saltsolution containing water, dibasic sodium phosphate (Na₂HPO₄) andmonobasic sodium phosphate (NaH₂PO₄). An enema containing this type ofcomposition is referred to as a “saline enema.” Typical amounts of theseingredients for unit dose administrations to adults are from 6.84 to7.56 grams dibasic sodium phosphate and from 18.24 to 20.16 gramsmonobasic sodium phosphate. The concentration of the dibasic sodiumphosphate may be from 0.02 to 0.10 grams per milliliter (g/mL), and theconcentration of the monobasic sodium phosphate may be from 0.10 to 0.25g/mL. In a typical phosphate enema liquid formulation, the concentrationof the dibasic sodium phosphate may be from 0.04 to 0.08 g/mL, and theconcentration of the monobasic sodium phosphate may be from 0.12 to 0.20g/mL. Preferably the concentration of the dibasic sodium phosphate isfrom 0.05 to 0.07 g/mL, and the concentration of the monobasic sodiumphosphate is from 0.14 to 0.18 g/mL. For enemas based on this typicalformulation, the unit dose for an adult may be from 85 to 130 mL, andthe total liquid volume may be from 100 to 150 mL. For enemas based onthis typical formulation, the unit dose for a child may be from 45 to 65mL, and the total liquid volume may be from 50 to 75 mL. Typical amountsof these ingredients for unit dose administrations to children are from3.42 to 3.78 grams dibasic sodium phosphate, and from 9.12 to 10.08grams monobasic sodium phosphate.

In another phosphate enema liquid formulation, the concentration of thedibasic sodium phosphate may be from 0.01 to 0.05 g/mL, and theconcentration of the monobasic sodium phosphate may be from 0.05 to 0.12g/mL. This formulation range is disclosed in co-pending U.S. patentapplication Ser. No. 10/846,488, filed May 13, 2004, entitled “LargeVolume Enema.” In the large volume phosphate enema liquid formulation,the concentration of the dibasic sodium phosphate preferably is from0.03 to 0.04 g/mL, and the concentration of the monobasic sodiumphosphate preferably is from 0.07 to 0.09 g/mL. For enemas based on thisformulation, the unit dose for an adult may be from 170 to 260 mL, andthe total liquid volume may be from 200 to 300 mL.

In another example, the enema liquid 120 is an aqueous suspension of4,4′-(2-pyridylmethylene)bisphenol diacetate (bisacodyl). Theconcentration of bisacodyl may be from 0.05 to 0.1 milligrams permilliliter (mg/mL), and preferably is from 0.2 to 0.4 mg/mL. Forbisacodyl enemas based on this formulation, the unit dose for an adultmay be from 25 to 35 mL, and the total liquid volume may be from 30 to45 mL.

In another example, the enema liquid 120 is mineral oil. For mineral oilenemas, the unit dose for an adult may be from 85 to 130 mL, and thetotal liquid volume may be from 100 to 150 mL.

FIG. 2 represents a bottle 200 including a body 210, a neck 220 and anopening 230. The body 210 has a length 212 and a width 214. The neck 220has a length 222, a proximal end 224 at the junction with the body 210,a distal end 226 at the opening 230, and optional screw threads 228. Theproximal end 224 of the neck has a width 225, and the distal end 226 ofthe neck has a width 227. The length 212 may be from 4 to 12 centimeters(cm), and the width 214 may be from 2.5 to 6 cm. The length 222 may befrom 2 to 5 cm, the width 225 may be from 1 to 3 cm, and the width 227may be from 0.7 to 2.5 cm. The width 227 corresponds to the diameter ofopening 230.

The bottle 200 preferably is a flexible material. Examples of flexiblematerials for the bottle 200 include polyethylene, polypropylene,polyisoprene, polybutadiene, ethylene-propylene-diene copolymers (EPDM),styrene-butadiene copolymers (SBR), butadiene-acrylonitrile copolymers(NBR, or Buna-N), neoprene elastomer (polychloroprene and itscopolymers), polyurethane elastomer, and silicone elastomer. Examples offlexible polyethylenes include LDPE, LLDPE and HDPE. Preferably theflexible material is latex-free and sterile. It may be desirable for thebottle to be transparent or translucent, permitting the liquid contentsto be viewed. It may be desirable for the bottle to contain printedinformation, such as brand information, instructions for use, and/or anexpiration date.

The opening 230 and the area of the neck 220 near the opening preferablyare sized and shaped to provide a liquid-tight seal with a nozzle, suchas nozzle 114 in FIG. 1. Optional screw threads 228 may coordinate withscrew threads inside the nozzle to secure the nozzle to the opening 230.It may be desirable for the opening 230 and the area of the neck 220near the opening to be configured uniformly for bottles that otherwisemay have a variety of shapes and sizes. Such a uniform configuration mayprovide for a single type of nozzle to be used with a variety ofdifferent bottles.

FIG. 3 represents a cross sectional view of a nozzle 300 including aproximal opening 310 having a width 312, an attachment region 320including optional screw threads 322, a distal opening 330, a tip region340 having a length 342 and a width 344, and a lumen 350. The proximalopening 310 and the attachment region 320 preferably are sized andshaped to provide a liquid-tight seal with an opening of a bottle, suchas opening 230 in FIG. 2. Optional screw threads 322 may coordinate withscrew threads on a bottle to secure the nozzle to the bottle opening.The length 342 of the tip region 340 preferably is long enough to placethe distal opening 330 within the colon of the patient. The length 342may be from 3 to 5 cm. The width 344 of the tip region 340 preferably issmall enough to provide insertion of the tip region through the rectumwithout discomfort to the patient. The width 344 preferably is smallerthan the width 312 of the proximal opening. The width 344 may be from0.3 to 1 cm. The lumen 350 is a passageway for displacement of a liquidfrom a bottle, such as bottle 200 in FIG. 2, through the distal opening330 of the nozzle. The nozzle 300 may be all one piece, or it maycontain two or more pieces.

FIG. 4 represents a cross sectional view of a nozzle 400 including acollar 410 and an extension 420 as two separate pieces that togetherform a lumen 430. The collar 410 includes a proximal opening 412, anattachment region 414 having optional screw threads 416, and a taperedend 418. The extension 420 includes a distal opening 422, a tip region424, and a flared end 426. The tapered end 418 and the flared end 426preferably fit together to form a liquid-tight seal.

FIG. 5 represents a cross sectional view of an enema 500 including anenema liquid 510 and a dispenser 520, and illustrating possiblepositions 501-506 of a valve within the dispenser. The dispenser 520includes a bottle 530 and a nozzle 540. The bottle 530 includes a body532, a neck 534 and an opening 536. The nozzle 540 includes a proximalopening 542, an attachment region 544, a distal opening 546, a tipregion 548 and a lumen 550. A valve may be positioned at any point alongthe dispenser 520 beyond the level of liquid 510. A valve may beattached to the bottle 530, such as at the junction 501 between the body532 and the neck 534, at a point 502 within the neck, or at a point 503at or near the opening 536. A valve may be attached to the nozzle 540,such as at a point 504 at or near the attachment region 544, at a point505 within the tip region 548, or at a point 506 at or near the distalopening 546. In one example, a valve may be attached to the opening 536of the bottle 530. In another example, a valve may be attached to thenozzle 540 such that the valve extends across the lumen 550.

An enema dispenser valve may be any object that inhibits flow of theliquid into or out of an enema dispenser. Referring to FIG. 5, the valveminimizes or prevents liquid flow from the bottle 530 through the distalopening 546 until a critical compression force is applied to the bottle530. Once the critical compression force is applied, the enema liquidcan flow through the valve and out of the dispenser. Preferably thecritical compression force is greater than the forces typicallyencountered during normal handling of the enema prior to administration.

The valve also minimizes or prevents liquid flow from the surroundingenvironment into the dispenser, which may have the possibility ofoccurring after administration of the enema liquid to a patient.Referring to FIG. 5, for example, the valve minimizes or prevents liquidflow from the distal opening 546 back into the bottle 530. Without thevalve, liquid might reflux back into the dispenser due to the pressureof the liquid in contact with the exterior of the dispenser and/or thevacuum created in the interior of the dispenser during the delivery ofthe enema liquid. Preferably the valve prevents the flow of liquid backinto the dispenser for combinations of external liquid pressure andinternal vacuum pressure typically encountered during normaladministration of the enema.

FIGS. 6A and 6B represent a valve 600 including a membrane 610 having aslit 620 of a length 622, a diameter 630, and a thickness 640. Themembrane 610 is a disc of flexible material. Examples of flexiblematerials for membrane 610 include polyisoprene, polybutadiene,ethylene-propylene-diene copolymers (EPDM), styrene-butadiene copolymers(SBR), butadiene-acrylonitrile copolymers (NBR, or Buna-N), neopreneelastomer (polychloroprene and its copolymers), polyurethane elastomer,and silicone elastomer. The flexibility of materials is quantified bythe Shore A durometer value, which is measured according to ASTM D224000. The membrane may have a hardness of less than 150 Shore A,preferably less than 100 Shore A, and more preferably from 40 to 80Shore A. Preferably the membrane is latex-free and sterile. For example,the membrane material may be sterilized by irradiation, by autoclavetreatment, or by exposure to ethylene oxide.

The slit 620 of the valve 600 has two sides that remain in contact untila critical force is applied to the dispenser. When the two sides of theslit are in contact, liquid flow through the slit is minimized orprevented. Preferably the two sides of the slit form a liquid-tight sealwhen in contact. When a sufficient liquid pressure contacts the slit,the two sides may separate, allowing the liquid to flow through thevalve. Preferably the slit permits liquid flow in only one direction,allowing flow from the dispenser when a critical force is applied, andpreventing flow back into the dispenser. The length 622 of the slit islimited by the diameter 630 of the valve. For example, the length 622may be from 10 to 90% of the diameter 630. Preferably the length 622 isfrom 40 to 80% of the diameter 630, and more preferably is from 50 to70% of the diameter 630. For a diameter 630 of at most 3 cm, the length622 preferably is from 0.1 to 2.5 cm, more preferably is from 0.7 to 2.0cm, and more preferably is about 1.3 cm.

The diameter 630 of the valve 600 is related to the internal diameter ofthe dispenser at the location of the valve. For a valve positioned inthe nozzle and in contact with the opening of the bottle, the diameter630 may be from 0.5 to 3 cm, preferably is from 1.5 to 2.5 cm, and morepreferably is about 2 cm.

The thickness 640 of the valve 600 may be at most 0.90 mm. Preferablythe thickness 640 is from 0.05 to 0.90 mm. More preferably the thickness640 is from 0.10 to 0.90 mm, more preferably is from 0.5 to 0.90 mm,more preferably is from 0.60 to 0.89 mm, and more preferably is from0.70 to 0.80 mm.

FIGS. 7A through 7E represent valves having different slitconfigurations. FIG. 7A represents valve 700 including two separateslits 702 and 704. FIG. 7B represents valve 710 including twointersecting slits 712 and 714. FIG. 7C represents valve 720 includingthree separate slits 722, 724 and 726. FIG. 7D represents valve 730including three intersecting slits 732, 734 and 736. FIG. 7E representsvalve 740 including four intersecting slits 742, 744, 746 and 748. Slitsthat do not intersect may be substantially parallel, or they may beoriented at an angle relative to each other.

A valve including a membrane, a slit, and a thickness of at most 0.90 mmmay provide a reduction in the force required to dispense an enemaliquid from an enema dispenser. This reduction in the force required todispense an enema liquid from the dispenser may be quantified in termsof the squeeze force of the enema. Squeeze force is measured by thefollowing test. An enema is placed horizontally in a holder secured to abase of a test stand. The holder is a longitudinal cross section of ahollow cylinder having a radius of curvature of 2 inches (5.08 cm), anarc of 130-degrees, a length of 5.875 inches (14.92 cm), and capped at aright angle at each end with a 130-degree section of a washer having anouter diameter of 2 inches (5.08 cm) and an inner diameter of 13/16 inch(2.06 cm). Examples of test stands include mechanical test stands,pneumatic test stands, motorized test stands, and digital test stands.Specific examples of test stands include those available from Chatillon®(AMTEK TCI Division, Largo, Fla.), Cole-Farmer® Instrument Company(Vernon Hills, Ill.), and Imada, Inc. (Northbrook, Ill.). The test standis equipped with a force gauge connected to a movable crosshead, wherethe crosshead is a rigid half-cylinder having a length of 3.25 inches(8.26 cm), a diameter of 2 inches (5.08 cm), and a chamfer on eachsemicircular end of 0.125 inch (0.318 cm) by 45 degrees. Examples offorce gauges include those that operate mechanically, electronically orelectro-mechanically, and may include an analog or a digital display ofthe force measurement. The nozzle of the enema is attached to one end ofa tube, with the other end placed in a graduated cylinder positionedbelow the holder. The crosshead is lowered at a rate of 2 inches perminute (5.08 cm/min) to contact and compress the enema. The forcemeasurements from the force gauge are recorded at the initiation of flowand at particular displaced volumes as measured in the graduatedcylinder.

The compression force applied to the enema may be measured at theinitiation of liquid flow. The compression force may also be measuredonce particular liquid volumes or percentages of the liquid volumeoriginally contained in the enema are displaced. If the squeeze force isexpressed as the compression force at a total displaced liquid volume,the units for squeeze force include lb-f@ x oz., Newtons@ x mL, anddynes@ x mL, where “x” is the total volume of liquid displaced at themeasured compression force. If the squeeze force is expressed as thecompression force at a percentage of displaced liquid volume, the unitsfor squeeze force include lb-f@ y %, Newtons@ y %, and dynes@ y %, where“y” is the volume of liquid displaced as a percentage of the totalvolume of liquid originally contained in the enema. Examples of volumepercentages at which compression measurements may be taken include 0%(flow initiation), 10%, 25%, 50%, 75% and 100% of the liquid volumeoriginally contained in the enema.

FIG. 8 is a graph of the average squeeze force measurements for salineenemas for adult use. These enemas contained a total volume of 133 mL,with a unit dose of 118 mL. Examples 1 and 2 below provide additionalexperimental details for these results. For the enemas made by the samemanufacturer, enemas having a valve thickness of 0.76 mm (FLEET 0.76)showed a reduction in squeeze force at 75 mL of 39% relative to enemashaving a valve thickness of 1.02 mm (FLEET 1.02). When compared to theother enemas made by different manufacturers and having a valvethickness of from 0.91-1.02 mm (GENERIC), the enemas having a valvethickness of 0.76 mm showed a reduction in squeeze force at 75 mL of43%. At least 50% of the unit dose was delivered with a force of 53Newtons (N) for the enemas having a valve thickness of 0.76 mm. Incontrast, delivery of at least 50% of the unit dose of the enemas madeby the same manufacturer and having a valve thickness of 1.02 mmrequired a force of 93 N, and delivery of at least 50% of the unit doseof the enemas made by different manufacturers required a force of 133 N.Liquid flow was initiated with a force of 2.6 N for the enemas having avalve thickness of 0.76 mm. In contrast, initiation of flow for theenemas made by the same manufacturer and having a valve thickness of1.02 mm required a force of 24 N, and initiation of flow for the enemasmade by different manufacturers required a force of 21 N.

FIG. 9 is a graph of the average squeeze force measurements for largevolume saline enemas for adult use. These enemas contained a totalvolume of 240 mL, with a unit dose of 190 mL. Examples 1 and 3 belowprovide additional experimental details for these results. Enemas havinga valve thickness of 0.64, 0.76 or 0.89 mm showed a reduction in squeezeforce at 120 mL of 39-41% relative to enemas having a valve thickness of1.02 mm. At least 50% of the unit dose was delivered with a force from38-43 N for the enemas having a valve thickness of 0.64-0.89 mm. Incontrast, delivery of at least 50% of the unit dose of the enemas havinga valve thickness of 1.02 mm required a force of 76 N. Liquid flow wasinitiated with a force of from 2-4 N for the enemas having a valvethickness of 0.64-0.89 mm. In contrast, initiation of flow for theenemas having a valve thickness of 1.02 mm required a force of 17 N.

FIG. 10 is a graph of the average squeeze force measurements for salineenemas for pediatric use. These enemas contained a total volume of 66mL, with a unit dose of 59 mL. Examples 1 and 4 below provide additionalexperimental details for these results. Enemas having a valve thicknessof 0.64, 0.76 or 0.89 mm showed a reduction in squeeze force at 40 mL of40-46% relative to enemas having a valve thickness of 1.02 mm. At least50% of the unit dose was delivered with a force from 50-53 N for theenemas having a valve thickness of 0.64-0.89 mm. In contrast, deliveryof at least 50% of the unit dose of the enemas having a valve thicknessof 1.02 mm required a force of 93 N. Liquid flow was initiated with aforce of from 10-20 N for the enemas having a valve thickness of0.64-0.89 mm. In contrast, initiation of flow for the enemas having avalve thickness of 1.02 mm required a force of 48 N.

FIG. 11 is a graph of the average squeeze force measurements forbisacodyl enemas for adult use. These enemas contained a total volume of37 mL, with a unit dose of 30 mL. Examples 1 and 5 below provideadditional experimental details for these results. Enemas having a valvethickness of 0.64, 0.76 or 0.89 mm showed squeeze force values that wereapproximately equivalent to or better than the squeeze force values forenemas having a valve thickness of 1.02 mm. In addition, the enemashaving a valve thickness of 0.76 mm showed a reduction in squeeze forceat all measured displaced volumes, relative to enemas having a valvethickness of 1.02 mm. At least 50% of the unit dose was delivered with aforce from 52-58 N for the enemas having a valve thickness of 0.64-0.89mm. In contrast, delivery of at least 50% of the unit dose of the enemashaving a valve thickness of 1.02 mm required a force of 67 N.

FIG. 12 is a graph of the average squeeze force measurements for mineraloil enemas for adult use. These enemas contained a total volume of 133mL, with a unit dose of 118 mL. Examples 1 and 6 below provideadditional experimental details for these results. Enemas having a valvethickness of 0.64, 0.76 or 0.89 mm showed squeeze force values that wereapproximately equivalent to or better than the squeeze force values forenemas having a valve thickness of 1.02 mm. In addition, the enemashaving a valve thickness of 0.76 mm showed a reduction in squeeze forceat all measured displaced volumes, relative to enemas having a valvethickness of 1.02 mm. Liquid flow was initiated with a force of from12-18 N for the enemas having a valve thickness of 0.64-0.89 mm. Incontrast, initiation of flow for the enemas having a valve thickness of1.02 mm required a force of 35 N.

When incorporated into an enema dispenser, a valve including a membrane,a slit, and a thickness of at most 0.90 mm may provide a reduction inthe force required to dispense an enema liquid from the dispenser. Thiseffect may be greater for saline enemas. Within the saline enema system,the reduction in squeeze force was provided for enemas containingdifferent dose sizes and/or containing different concentrations of thephosphate ingredients. A valve including a membrane having a slit and athickness of from 0.70-0.80 mm may reduce the force required toadminister a variety of enema liquids relative to an enema containing aconventional valve.

The advantageous reduction in squeeze force for an enema having a valveincluding a membrane, a slit, and a thickness of at most 0.90 mm may beprovided without permitting reflux of liquid back into the dispenserafter use. In addition, the advantageous reduction in squeeze force maybe provided without permitting leakage of the liquid prior to use. Itmay be desirable for the thickness to be at least a minimum thickness,so as to ensure this prevention of reflux and leakage. Examples ofminimum thicknesses include 0.05 mm, 0.10 mm, 0.60 mm and 0.70 mm.

The resistance of an enema dispenser to reflux of liquid back into thedispenser is measured by the following test. An enema is placedhorizontally in a bath of water containing a dye, with the nozzle belowthe liquid surface. The enema bottle is squeezed by hand to expel aliquid volume corresponding to a unit dose of the enema liquid. The handpressure is then released, with the nozzle maintained beneath the liquidsurface, and the dispenser is observed for any colored water being drawninto the dispenser. The squeezing, releasing and observation steps arerepeated four more times or until all liquid has been expelled from thedispenser.

Referring again to FIGS. 8 through 12, all of the enemas were tested forreflux, except for the “GENERIC” enemas. All of the enemas tested showedno evidence of reflux. Even though the thinner valves may have reducedthe squeeze force of enemas, the valves did not permit reflux flow ofliquid back into the enema dispenser. Thus, an improvement in enemasqueeze force may be obtained without impairing the desirable refluxprevention characteristic.

FIG. 13 represents a method 800 of bowel cleansing, including insertingan enema having a bottle, a liquid in the bottle, and a nozzle into arectum 810, and applying a compression force to the enema bottle 820.Referring to FIG. 1, the nozzle 114 of the enema dispenser 110 may beinserted into the rectum of a patient. The bottle 112 may then becompressed to displace the enema liquid 120 in the bottle through thenozzle 114 and into the colon of the patient. The compression of thebottle may be accomplished by squeezing the bottle by hand, either bythe patient or by a separate user.

The following examples are provided to illustrate one or more preferredembodiments of the invention. Numerous variations may be made to thefollowing examples that lie within the scope of the invention.

EXAMPLES Example 1 Squeeze Force and Reflux Measurement Procedure

A Chatilion® UTSM-HS-FS test stand was equipped with a Chatillon® DFM-50force gauge. The crosshead was an aluminum half-cylinder having a lengthof 3.25 inches (8.26 cm) and a diameter of 2 inches (5.08 cm). Eachsemicircular end had a chamfer of 0.125 inch (0.318 cm) by 45 degrees.The crosshead was attached to the test stand through a 10-32 hole in thecenter of the crosshead. The test stand was also equipped with a holderfor a bottle. The holder was a longitudinal cross-section of a hollowstainless steel cylinder having an original diameter of 2 inches (5.08cm). The arc of the partial cylinder was 130-degrees. The length of theholder was 5.875 inches (14.92 cm), and each end was connected to a130-degree section of a stainless steel washer having an outer diameterof 2 inches (5.08 cm) and an inner diameter of 13/16 inch (2.06 cm). Thepartial washers were at right angles to the partial cylinder wall. Theholder was affixed to the base of the test stand by a 0.375 inch (0.953cm) thick stainless steel adaptor plate having a length of 4.5 inches(11.43 cm) and a width of 3 inches (7.62 cm). The holder was centered onthe plate and perpendicular with respect to the length of the plate. Theplate had two ¼-20 holes, each positioned 0.5 inch (1.27 cm) from an endof the plate and centered 1.5 inches (3.81 cm) from each side of theplate. The plate was affixed to the base of the test stand by screwspassing through each of these holes.

This apparatus was used to measure squeeze force of enemas. An enema wasplaced horizontally in the holder, and one end of a flexible tube wasattached to the end of the enema nozzle. The other end of the flexibletube was placed in a graduated cylinder, which was positioned below theholder. The test stand was programmed to lower the crosshead at a rateof 2 inches per minute (5.08 cm/min). The force measurements wererecorded at the initiation of flow and at particular displaced volumesas measured in the graduated cylinder.

The resistance of enemas to reflux was measured by the followingprocedure. An enema was placed horizontally in a bath of watercontaining a dye, with the nozzle below the liquid surface. The enemabottle was squeezed by hand to expel a liquid volume corresponding to aunit dose of the enema liquid. The hand pressure was then released, withthe nozzle maintained beneath the liquid surface, and the dispenser wasobserved for any colored water being drawn into the dispenser. Thesqueezing, releasing and observation steps were repeated four more timesor until all liquid had been expelled from the dispenser.

Example 2 Adult Saline Enemas

A series of saline enemas for adult use were examined using theprocedures of Example 1. The saline enemas each contained 133 mL of anaqueous solution of dibasic sodium phosphate (0.06 g/mL) and monobasicsodium phosphate (0.16 g/mL). Of the 133 mL of total liquid, 118 mL isconsidered a unit dose. For the squeeze force testing, forcemeasurements were recorded at the initiation of flow and at displacedvolumes of 15 mL, 30 mL, 45 mL, 60 mL and 75 mL as measured in thegraduated cylinder.

FLEET® saline enemas were equipped with membrane valves having adiameter of 0.778 inch (1.98 cm), a single slit having a length of 0.485inch (1.23 cm), and a thickness either of 1.02 mm (“FLEET 1.02”) or of0.76 mm (“FLEET 0.76”). The membrane valves were made of a sterileelastomer having a hardness of from 66-76 Shore A. For these enemas, thesqueeze force measurement was repeated for a total of 20 samples foreach type of enema. Saline enemas from other manufacturers (“GENERIC”)were equipped with membrane valves having a diameter of 0.778 inch (1.98cm), a single slit having a length of 0.485 inch (1.23 cm), and athickness from 0.91-1.02 mm. The squeeze force measurement was repeatedfor a total of 12 samples. FIG. 8 is a graph of the average squeezeforce measurements for these enemas. One sample of each type of enemawas also tested for reflux. No reflux was observed for any of the enemastested.

Example 3 Large Volume Adult Saline Enemas

A series of FLEET® large volume saline enemas for adult use wereequipped with membrane valves having a diameter of 1.98 cm, a singleslit having a length of 1.23 cm, and a thickness of 1.02, 0.89, 0.76 or0.64 mm. The membrane valves were made of a sterile elastomer having ahardness of from 66-76 Shore A. Each enema contained 240 mL of anaqueous solution of dibasic sodium phosphate (0.03 g/mL) and monobasicsodium phosphate (0.8 g/mL). Of the 240 mL of total liquid, 190 mL isconsidered a unit dose. These enemas were tested for squeeze force bythe procedure of Example 1, with force measurements recorded at theinitiation of flow and at displaced volumes of 20 mL, 40 mL, 60 mL, 80mL, 100 mL and 120 mL as measured in the graduated cylinder. The squeezeforce measurement was repeated for a total of 20 samples for each typeof enema. FIG. 9 is a graph of the average squeeze force measurementsfor these enemas. One sample of each type of enema was also tested forreflux. No reflux was observed for any of the enemas tested.

Example 4 Pediatric Adult Saline Enemas

A series of FLEET® saline enemas for pediatric use were equipped withmembrane valves having a diameter of 1.98 cm, a single slit having alength of 1.23 cm, and a thickness of 1.02, 0.89, 0.76 or 0.64 mm. Themembrane valves were made of a sterile elastomer having a hardness offrom 66-76 Shore A. Each enema contained 66 mL of an aqueous solution ofdibasic sodium phosphate (0.06 g/mL) and monobasic sodium phosphate(0.16 g/mL). Of the 66 mL of total liquid, 59 mL is considered a unitdose. These enemas were tested for squeeze force by the procedure ofExample 1, with force measurements recorded at the initiation of flowand at displaced volumes of 10 mL, 20 mL, 30 mL and 40 mL as measured inthe graduated cylinder. The squeeze force measurement was repeated for atotal of 3 samples for each type of enema. FIG. 10 is a graph of theaverage squeeze force measurements for these enemas. One sample of eachtype of enema was also tested for reflux. No reflux was observed for anyof the enemas tested.

Example 5 Adult Bisacodyl Enemas

A series of FLEET® bisacodyl enemas for adult use were equipped withmembrane valves having a diameter of 1.98 cm, a single slit having alength of 1.23 cm, and a thickness of 1.02, 0.89, 0.76 or 0.64 mm. Themembrane valves were made of a sterile elastomer having a hardness offrom 66-76 Shore A. Each enema contained 37 mL of an aqueous suspensionof bisacodyl (0.33 mg/mL), and of the 37 mL of total liquid, 30 mL isconsidered a unit dose. These enemas were tested for squeeze force bythe procedure of Example 1, with force measurements recorded at theinitiation of flow and at displaced volumes of 5 mL, 10 mL, 15 mL and 20mL as measured in the graduated cylinder. The squeeze force measurementwas repeated for a total of 3 samples for each type of enema. FIG. 11 isa graph of the average squeeze force measurements for these enemas. Onesample of each type of enema was also tested for reflux. No reflux wasobserved for any of the enemas tested.

Example 6 Adult Mineral Oil Enemas

A series of FLEET® mineral oil enemas for adult use were equipped withmembrane valves having a diameter of 1.98 cm, a single slit having alength of 1.23 cm, and a thickness of 1.02, 0.89, 0.76 or 0.64 mm. Themembrane valves were made of a sterile elastomer having a hardness offrom 66-76 Shore A. Each enema contained 133 mL of total liquid, ofwhich 118 mL is considered a unit dose. These enemas were tested forsqueeze force by the procedure of Example 1, with force measurementsrecorded at the initiation of flow and at displaced volumes of 15 mL, 30mL, 45 mL, 60 mL and 75 mL as measured in the graduated cylinder. Thesqueeze force measurement was repeated for a total of 3 samples for eachtype of enema. FIG. 12 is a graph of the average squeeze forcemeasurements for these enemas. One sample of each type of enema was alsotested for reflux. No reflux was observed for any of the enemas tested.

While various embodiments of the invention have been described, it willbe apparent to those of ordinary skill in the art that other embodimentsand implementations are possible within the scope of the invention.Accordingly, the invention is not to be restricted except in light ofthe attached claims and their equivalents.

What is claimed is:
 1. An enema, comprising: a bottle comprising abottle opening; a nozzle, attached to the bottle at the bottle opening,and comprising a distal opening; a valve comprising a membrane having aslit; a protective shield on the nozzle; and a liquid in the bottlehaving total volume of 100 to 150 mL; wherein at least a portion of theliquid can be dispensed through the distal opening when the bottle iscompressed with a force of at most 20 Newtons; the liquid comprises aunit dose of an aqueous mixture comprising dibasic sodium phosphate andmonobasic sodium phosphate; and the membrane has a thickness from 0.05to 0.90 mm.
 2. The enema of claim 1, wherein at least a portion of theliquid can be dispensed through the distal opening when the bottle iscompressed with a force of at most 10 Newtons.
 3. The enema of claim 1,wherein at least a portion of the liquid can be dispensed through thedistal opening when the bottle is compressed with a force of at most 5Newtons.
 4. The enema of claim 1, wherein the unit dose comprises from6.84 to 7.56 grams dibasic sodium phosphate and from 18.24 to 20.16grams monobasic sodium phosphate.
 5. The enema of claim 4, wherein atleast 50% of the unit dose can be dispensed from the distal opening whenthe bottle is compressed with a force of at most 80 Newtons.
 6. Theenema of claim 1, wherein the membrane has 2 slits.
 7. The enema ofclaim 4, wherein the membrane has a thickness from 0.50 to 0.90 mm. 8.The enema of claim 5, wherein the membrane has a thickness from 0.50 to0.90 mm.
 9. The enema of claim 7, wherein the membrane has 2 slits. 10.The enema of claim 1, wherein the valve is sterile.
 11. The enema ofclaim 1, wherein the unit dose is 85 to 130 mL of the liquid.
 12. Anenema, comprising: a bottle comprising a bottle opening; nozzle,attached to the bottle at the bottle opening, and comprising a distalopening; a valve comprising a membrane having a slit; a protectiveshield on the nozzle; and a liquid in the bottle having total volume of100 to 150 mL; the liquid comprises a unit dose of an aqueous mixturecomprising dibasic sodium phosphate and monobasic sodium phosphate;wherein at least 50% of the unit dose can be dispensed through thedistal opening when the bottle is compressed with a force of at most 80Newtons; and the membrane has a thickness from 0.05 to 0.90 mm.
 13. Theenema of claim 12, wherein the membrane has a plurality of slits. 14.The enema of claim 12, wherein the membrane has 2 slits.
 15. The enemaof claim 12, wherein the membrane has a thickness from 0.50 to 0.90 mm.16. The enema of claim 14, wherein the membrane has a thickness from0.50 to 0.90 mm.
 17. The enema of claim 12, wherein the unit dosecomprises from 6.84 to 7.56 grams dibasic sodium phosphate and from18.24 to 20.16 grams monobasic sodium phosphate.
 18. The enema of claim14, wherein the unit dose comprises from 6.84 to 7.56 grams dibasicsodium phosphate and from 18.24 to 20.16 grams monobasic sodiumphosphate.
 19. The enema of claim 16, wherein the unit dose comprisesfrom 6.84 to 7.56 grams dibasic sodium phosphate and from 18.24 to 20.16grams monobasic sodium phosphate.
 20. The enema of claim 12, wherein thevalve is sterile.
 21. The enema of claim 12, wherein the unit dose is 85to 130 mL of the liquid.